The 4th Annual Symposium of the Intrinsically Disordered Proteins (IDP) Subgroup of the Biophysical Society will be held February 20, 2010, at the San Francisco Convention Center, San Francisco, California. The theme of the Symposium is Regulation and Utilization of Protein Disorder In Vivo. The program Co-Chairs, Elisar Barbar (Oregon State University) and Huang-Xiang Zhou (Florida State University) have developed an outstanding program, which includes nine invited speakers from the US, Canada, England, and Israel. Speakers include senior leaders in the field of IDPs as well as junior scientists who are having high impact in the field. In addition, two postdoctoral research awardees will be selected to speak at the Symposium. The traditional view of protein structure-function relationships posits a well-defined three-dimensional (3D) structure is required for function. However, it is now well appreciated that many biological functions are performed by highly dynamic proteins or protein domains that, in isolation, lack secondary and/or tertiary structure under physiological conditions. These proteins, termed intrinsically disordered proteins (IDPs), exist in organisms from all kingdoms of life and are most prevalent in eukaryotes. In mammals, IDPs mediate diverse cellular processes, including motility, metabolism and biosynthesis, division, and gene transcription. A point of special relevance to NIH is that IDPs are overrepresented in association with numerous human diseases such as cancer and neurodegenerative diseases. The tools traditionally used for determination of rigid protein structures are generally unsuitable in studies of IDPs due to their highly dynamic and disordered nature. However, NMR techniques which allow studies of dynamic protein ensembles have been adapted for studies of IDPs, as have other techniques such as small- angle X-ray scattering and single-molecule techniques. In addition, a wide variety of computational methods have emerged as powerful tools in studies of IDPs. The IDP Subgroup Annual Symposium has emerged as a leading forum for discussion of methodologies best suited for detailed studies of IDPs. The pace of studies of disordered proteins has been slow relative to output from projects such as the Protein Structure Initiative in the US, which is focused on highly ordered (folded) proteins. This has created a knowledge gap with respect to relationships between the structural and dynamic properties of thousands of IDPs (in humans) and the mechanisms that mediate their biological functions. Through its Annual Symposium, the IDP Subgroup seeks to develop and broaden awareness of new knowledge related to IDPs and new techniques for the characterization of their structure, dynamics, and biological functions. Support for this Symposium will reduce the knowledge gap noted above and promote everyone's long-range goal of improving treatment options for patients with cancer and other IDP-associated diseases. A major goal associated with this request for R13 funding is to provide support for young scientists to participate in the IDP Subgroup Annual Symposium, including two graduate students and four postdoctoral researchers. The IDP Subgroup and the Biophysical Society encourage participation of women, racial/ethnic minorities, persons with disabilities, and other individuals who traditionally have been underrepresented in science. PUBLIC HEALTH RELEVANCE: IDPs are involved in the pathogenesis of many human diseases, including cancer and neurodegenerative diseases. Therefore, expanding our knowledge of the structural features and functional mechanisms of IDPs through support of the IDP Subgroup Annual Symposium will provide insights into diverse biological processes. Furthering studies of IDPs will also drive new discoveries regarding the molecular mechanisms associated with devastating human diseases and provide new directions for therapeutics to combat these diseases.